α-Synuclein fibrils subvert lysosome structure and function for the propagation of protein misfolding between cells through tunneling nanotubes.

Among over 150 distinct RNA modifications, N6-methyladenosine (m6A) and adenosine-to-inosine (A-to-I) RNA editing represent 2 of the most studied modifications on mammalian mRNAs. Although both modifications occur on adenosine residues, knowledge on potential functional crosstalk between these 2 mod...

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Autores principales:	Hideki Terajima, Mijia Lu, Linda Zhang, Qi Cui, Yanhong Shi, Jianrong Li, Chuan He
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6b70eecb7a0b450fa7b86a323b5aaee8
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spelling	oai:doaj.org-article:6b70eecb7a0b450fa7b86a323b5aaee82021-12-02T19:54:21Zα-Synuclein fibrils subvert lysosome structure and function for the propagation of protein misfolding between cells through tunneling nanotubes.1544-91731545-788510.1371/journal.pbio.3001292https://doaj.org/article/6b70eecb7a0b450fa7b86a323b5aaee82021-07-01T00:00:00Zhttps://doi.org/10.1371/journal.pbio.3001292https://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Among over 150 distinct RNA modifications, N6-methyladenosine (m6A) and adenosine-to-inosine (A-to-I) RNA editing represent 2 of the most studied modifications on mammalian mRNAs. Although both modifications occur on adenosine residues, knowledge on potential functional crosstalk between these 2 modifications is still limited. Here, we show that the m6A modification promotes expression levels of the ADAR1, which encodes an A-to-I RNA editing enzyme, in response to interferon (IFN) stimulation. We reveal that YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) mediates up-regulation of ADAR1; YTHDF1 is a reader protein that can preferentially bind m6A-modified transcripts and promote translation. Knockdown of YTHDF1 reduces the overall levels of IFN-induced A-to-I RNA editing, which consequently activates dsRNA-sensing pathway and increases expression of various IFN-stimulated genes. Physiologically, YTHDF1 deficiency inhibits virus replication in cells through regulating IFN responses. The A-to-I RNA editing activity of ADAR1 plays important roles in the YTHDF1-dependent IFN responses. Therefore, we uncover that m6A and YTHDF1 affect innate immune responses through modulating the ADAR1-mediated A-to-I RNA editing.Hideki TerajimaMijia LuLinda ZhangQi CuiYanhong ShiJianrong LiChuan HePublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 19, Iss 7, p e3001292 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Hideki Terajima Mijia Lu Linda Zhang Qi Cui Yanhong Shi Jianrong Li Chuan He α-Synuclein fibrils subvert lysosome structure and function for the propagation of protein misfolding between cells through tunneling nanotubes.
description	Among over 150 distinct RNA modifications, N6-methyladenosine (m6A) and adenosine-to-inosine (A-to-I) RNA editing represent 2 of the most studied modifications on mammalian mRNAs. Although both modifications occur on adenosine residues, knowledge on potential functional crosstalk between these 2 modifications is still limited. Here, we show that the m6A modification promotes expression levels of the ADAR1, which encodes an A-to-I RNA editing enzyme, in response to interferon (IFN) stimulation. We reveal that YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) mediates up-regulation of ADAR1; YTHDF1 is a reader protein that can preferentially bind m6A-modified transcripts and promote translation. Knockdown of YTHDF1 reduces the overall levels of IFN-induced A-to-I RNA editing, which consequently activates dsRNA-sensing pathway and increases expression of various IFN-stimulated genes. Physiologically, YTHDF1 deficiency inhibits virus replication in cells through regulating IFN responses. The A-to-I RNA editing activity of ADAR1 plays important roles in the YTHDF1-dependent IFN responses. Therefore, we uncover that m6A and YTHDF1 affect innate immune responses through modulating the ADAR1-mediated A-to-I RNA editing.
format	article
author	Hideki Terajima Mijia Lu Linda Zhang Qi Cui Yanhong Shi Jianrong Li Chuan He
author_facet	Hideki Terajima Mijia Lu Linda Zhang Qi Cui Yanhong Shi Jianrong Li Chuan He
author_sort	Hideki Terajima
title	α-Synuclein fibrils subvert lysosome structure and function for the propagation of protein misfolding between cells through tunneling nanotubes.
title_short	α-Synuclein fibrils subvert lysosome structure and function for the propagation of protein misfolding between cells through tunneling nanotubes.
title_full	α-Synuclein fibrils subvert lysosome structure and function for the propagation of protein misfolding between cells through tunneling nanotubes.
title_fullStr	α-Synuclein fibrils subvert lysosome structure and function for the propagation of protein misfolding between cells through tunneling nanotubes.
title_full_unstemmed	α-Synuclein fibrils subvert lysosome structure and function for the propagation of protein misfolding between cells through tunneling nanotubes.
title_sort	α-synuclein fibrils subvert lysosome structure and function for the propagation of protein misfolding between cells through tunneling nanotubes.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/6b70eecb7a0b450fa7b86a323b5aaee8
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α-Synuclein fibrils subvert lysosome structure and function for the propagation of protein misfolding between cells through tunneling nanotubes.

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